Mono6: Activity of Valomaciclovir in Infectious Mononucleosis Due to Primary Epstein-Barr Virus Infection

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00575185
• Collaborator: Epiphany Biosciences (Industry)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This will be a randomized, placebo-controlled, double-blind single-center proof of concept study to evaluate the anti-EBV activity of 4 grams of valomaciclovir (2 grams BID) for 21 days in subjects with infectious mononucleosis documented to be caused by primary EBV infection. Otherwise healthy subjects (≥15 years old) referred to us with a clinical diagnosis of primary infectious mononucleosis will be screened and those with laboratory-confirmed primary EBV infection will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
Infectious Mononucleosis	Drug: Valomaciclovir; Drug: placebo	Phase 1/Phase 2

Detailed Description

Subjects will be seen 2 times a week for 3 weeks and then weekly for 3 weeks. Clinical findings, clinical lab tests, EBV viral loads, and EBV antibody titers will be obtained at each clinic visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Placebo-Controlled, Double-Blind Study to Assess Clinical and Antiviral Activity of Valomaciclovir (EPB 348) in Infectious Mononucleosis Due to Primary Epstein-Barr Virus Infection (Mono 6)
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Valomaciclovir Valomaciclovir 2 grams orally twice daily for 21 days	Drug: Valomaciclovir; 4 grams orally of valomaciclovir (2 grams BID) for 21 days.
Placebo Comparator: placebo placebo 2 tablets twice daily for 21 days	Drug: placebo; Placebo tablets orally twice daily for 21 days.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Improvement in Clinical Symptoms and Reductions in Viral Burden From Baseline [21 days]

   All subjects had confirmed cases of EB and will be assessed for Improvement of clinical symptoms (ie: tiredness, nausea etc)and reduction in viral burden from baseline

Secondary Outcome Measures

1. Number of Participants Who Experienced Adverse Events During the Study Safety and Tolerability [15 days]

   Assessing adverse events in participants to see if this drug causes more or less side effects

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 15 years or older

• Within 14 days of initial symptoms of present illness diagnosed by a health care provider as infectious mononucleosis and confirmed to be due to primary EBV by antibody profile. The criteria for antibody confirmation of primary EBV at the screening visit are: 1)Positive for anti-EBV VCA IgM antibody and negative for anti-EBV EBNA1 IgG antibody; 2)EBV antibody testing will be done in the Clinical Virology Research Laboratory using commercial ELISA kits (Diamedix Corporation, Miami, FL).

• Willingness to sign the Informed Consent Form (ICF)

• Willingness to contribute samples of blood and oral washings at regular intervals

• Males and females must use effective contraception during treatment and for at least 90 days following treatment

• Negative pregnancy test result at the Screening Visit for females of childbearing potential (including females who have had a bilateral tubal ligation). Female patients of childbearing potential must be willing to use an approved method of double-barrier contraception (hormonal plus barrier or barrier plus barrier, eg, diaphragm plus condom) from the time of first dose administration until 90 days after completion of dosing and male patients with female partners of childbearing potential must be willing to use a condom. Patients who are sterile or infertile (defined as those who are postmenopausal or have undergone a complete hysterectomy) are eligible.

• Estimated creatinine clearance (Cockcroft and Gault method) ≥ 60 ml/min

• Absolute neutrophil count ≥ 1000 cells/microliter

• Platelets ≥ 100,000/microliter

• Hemoglobin ≥ 9.5 g/dL

Exclusion Criteria:

• Previous history of infectious mononucleosis-like illness

• Immunosuppressed due to medical disease and/or immunosuppressive or immunomodulating medications (e.g., corticosteroids prior to enrollment, cytotoxic drugs, interferons)

• Another intercurrent viral infection (including HIV), based on history or referring physician medical evaluation

• More than 7 days elapsed since onset of illness (including screening time)

• The following concomitant medications are prohibited: probenecid, trimethoprim, myelosuppressive therapies, and medications known to be nephrotoxic

• Breast feeding during the study

• Corticosteroids are not permitted. If they are prescribed by the subject's primary physician for treatment of this acute disease after the subject has enrolled, the subject will be replaced.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• University of Minnesota
• Epiphany Biosciences

Investigators

• Principal Investigator: Henry H Balfour, MD, Professor of Laboratory Medicine & Pathology, and Pediatrics

Study Documents (Full-Text)

None provided.

More Information

Publications

• Balfour HH Jr, Hokanson KM, Schacherer RM, Fietzer CM, Schmeling DO, Holman CJ, Vezina HE, Brundage RC. A virologic pilot study of valacyclovir in infectious mononucleosis. J Clin Virol. 2007 May;39(1):16-21. Epub 2007 Mar 21.
• Balfour HH Jr, Holman CJ, Hokanson KM, Lelonek MM, Giesbrecht JE, White DR, Schmeling DO, Webb CH, Cavert W, Wang DH, Brundage RC. A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis. J Infect Dis. 2005 Nov 1;192(9):1505-12. Epub 2005 Sep 26.
• Cameron B, Galbraith S, Zhang Y, Davenport T, Vollmer-Conna U, Wakefield D, Hickie I, Dunsmuir W, Whistler T, Vernon S, Reeves WC, Lloyd AR; Dubbo Infection Outcomes Study. Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis. J Infect Dis. 2007 Jul 1;196(1):56-66. Epub 2007 May 24.
• Hislop AD, Kuo M, Drake-Lee AB, Akbar AN, Bergler W, Hammerschmitt N, Khan N, Palendira U, Leese AM, Timms JM, Bell AI, Buckley CD, Rickinson AB. Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host balance. J Clin Invest. 2005 Sep;115(9):2546-55. Epub 2005 Aug 18.
• Hislop AD, Taylor GS, Sauce D, Rickinson AB. Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. Annu Rev Immunol. 2007;25:587-617. Review.
• Rea TD, Russo JE, Katon W, Ashley RL, Buchwald DS. Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. J Am Board Fam Pract. 2001 Jul-Aug;14(4):234-42.
• Silins SL, Sherritt MA, Silleri JM, Cross SM, Elliott SL, Bharadwaj M, Le TT, Morrison LE, Khanna R, Moss DJ, Suhrbier A, Misko IS. Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load. Blood. 2001 Dec 15;98(13):3739-44.
• Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis. 1999;31(6):543-7.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT00575185
• Other Study ID Numbers: 0709M16341
• First Posted: Dec 18, 2007
• Last Update Posted: Mar 22, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by University of Minnesota: Mono; Mononucleosis; Epstein-Barr virus
• Additional relevant MeSH terms: Infections; Virus Diseases; Communicable Diseases; Epstein-Barr Virus Infections; Infectious Mononucleosis

Study Results

Participant Flow

Recruitment Details	University of Minnesota students that contracted Mono and wsere seen at the student health center

Arm/Group Title	Valomaciclovir	Placebo
Arm/Group Description	Valomaciclovir 2 grams orally twice daily for 21 days Valomaciclovir : 4 grams orally of valomaciclovir (2 grams BID) for 21 days.	placebo 2 tablets twice daily for 21 days placebo : Placebo tablets orally twice daily for 21 days.
Period Title: Overall Study
STARTED	12	11
COMPLETED	12	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Valomaciclovir	Placebo	Total
Arm/Group Description	Valomaciclovir 2 grams orally twice daily for 21 days Valomaciclovir : 4 grams orally of valomaciclovir (2 grams BID) for 21 days.	placebo 2 tablets twice daily for 21 days placebo : Placebo tablets orally twice daily for 21 days.	Total of all reporting groups
Overall Participants	12	11	23
Age, Customized (particpants) [Number]
<=18 years	0	0	0
Between 18 and 65 years	12	11	23
>=65 years	0	0	0
Sex: Female, Male (Count of Participants)
Female	5 41.7%	5 45.5%	10 43.5%
Male	7 58.3%	6 54.5%	13 56.5%
Region of Enrollment (participants) [Number]
United States	12 100%	11 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Improvement in Clinical Symptoms and Reductions in Viral Burden From Baseline
Description	All subjects had confirmed cases of EB and will be assessed for Improvement of clinical symptoms (ie: tiredness, nausea etc)and reduction in viral burden from baseline
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valomaciclovir	Placebo
Arm/Group Description	Valomaciclovir 2 grams orally twice daily for 21 days Valomaciclovir : 4 grams orally of valomaciclovir (2 grams BID) for 21 days.	placebo 2 tablets twice daily for 21 days placebo : Placebo tablets orally twice daily for 21 days.
Measure Participants	12	11
Number [participants]	12 100%	11 100%

2. Secondary Outcome

Title	Number of Participants Who Experienced Adverse Events During the Study Safety and Tolerability
Description	Assessing adverse events in participants to see if this drug causes more or less side effects
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valomaciclovir	Placebo
Arm/Group Description	Valomaciclovir 2 grams orally twice daily for 21 days Valomaciclovir: 4 grams orally of valomaciclovir (2 grams BID) for 21 days.	placebo 2 tablets twice daily for 21 days placebo: Placebo tablets orally twice daily for 21 days.
Measure Participants	12	11
Number [participants]	12 100%	11 100%

Adverse Events

Arm/Group Title	Valomaciclovir		Placebo
Arm/Group Description	Valomaciclovir 2 grams orally twice daily for 21 days Valomaciclovir : 4 grams orally of valomaciclovir (2 grams BID) for 21 days.		placebo 2 tablets twice daily for 21 days placebo : Placebo tablets orally twice daily for 21 days.
All Cause Mortality
	Valomaciclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Valomaciclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/11 (0%)
Endocrine disorders
Pancreatitis	1/12 (8.3%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Valomaciclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/12 (58.3%)		5/11 (45.5%)
Gastrointestinal disorders
Abdominal Pain	6/12 (50%)	6	5/11 (45.5%)	5
Nausea	7/12 (58.3%)	7	1/11 (9.1%)	1
Vomiting	3/12 (25%)	3	0/11 (0%)	0
Nervous system disorders
Headache	4/12 (33.3%)	4	5/11 (45.5%)	5
Skin and subcutaneous tissue disorders
Rash	2/12 (16.7%)	2	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.